Pigs are Key for Organ Transplants — But Why?

A pig’s kidney was transplanted into a man’s body over 40 days ago, the longest an experiment like this has gone on. The man, who is from New York, is brain-dead, and his family has agreed to let the trial continue through mid-September.

It’s a scientific breakthrough that brings humans a step closer to using pig organs for people who desperately need transplants and have run out of time waiting for human organs. Over 5,000 people on transplant lists die every year, according to the Health Resources and Services Administration.

Interspecies transplants, or xenotransplantation, is the most promising way to decrease these deaths, eventually. It’s a slow process and has taken decades to reach this point, where the most likely outcome is still organ failure or rejection.

But why pigs? Wouldn’t an animal that’s more like a human, like a primate, be a better fit?

Muhammad M. Mohiuddin, M.D., Director at the Cardiac Xenotransplantation Program at the University of Maryland School of Medicine, who was part of last year’s groundbreaking pig-to-human heart transplant says, initially, pigs weren’t the preferred species, but now they’re our best bet.

From baboons to pigs

In the initial xenotransplant experiments, chimpanzee or baboon organs were used, Dr. Mohiuddin tells The Messenger. “The major reason in deviating from non-human primates to pigs was the disease transmission that had occurred using the baboon organs.”

Diseases, including HIV, can be transmitted from primates to humans, and some baboons are now endangered species. And their likeness to humans is, in some ways, a drawback.

“It takes about 20 years for a non-human primate to get to a size where an organ can be compatible with an adult human,” Dr. Mohiuddin says. And the primate gestation period is as long as humans at nine months, and like people, they tend to give birth to only one infant at a time. 

But pigs have a gestation period that’s just under four months and can have 7-14 pigs per litter, and two litters per year. “And they grow very fast. So within a year, the size of a pig is compatible with what we need for a human,” he adds.

Further, scientists  know the entire genome of the pig, and can alter it. They can take out genes that induce a human immune response to reject the organ; they can remove antigens expressed on pig cells that could likewise prompt an unwanted immune response.

After the heart transplant last year performed by Dr. Mohiuddin’s team, the patient, who was alive at the time of the transfer, died after two months from heart failure, but the doctors were able to avoid “hyperacute rejection,” which he describes as when “the heart is rejected immediately. You see the heart turning black right in front of your eyes.”

Because of the human body’s ability to immediately recognize the pig’s organ as foreign and quickly produce antibodies to kill it, scientists have had to remove the antigens from the pig that are inducing that response.

“We are trying to make sure everything we have discovered that prevents us from having a long-term graft survival is either taken out or exchanged with a human gene,” Dr. Mohiuddin says. 

“It’s not the correct way of saying it,” he adds. “But we are trying to humanize the pig.”

Dr. Mohiuddin is referring to making the pig’s genome more like a human’s, but he recognizes the many ethical questions that xenotransplantation raises for both humans and animals.

“There are many [ethical concerns], but I've taken an oath to save lives,” he says. “So my goal is to have a valid option for all of these people — I receive emails and phone calls continuously from patients who are volunteering themselves for an experimental transplant because they have no other option.” 

Tricky ethical questions

In response to the news of his team’s transplant, People for the Ethical Treatment of Animals (PETA) released a statement calling the experiment “unethical and dangerous.”

“Animals aren’t tool sheds to be raided but complex, intelligent beings. It would be better for them and healthier for humans to leave them alone and seek cures using modern science,” the statement reads in part.

The pigs used for xenotransplant experiments at various universities all come from the same company,  Revivicor. Previously known as PPL therapeutics, Revivicor worked with the Roslin Institute to clone the first mammal in 1996, Dolly the sheep, and to clone the first pigs in 2000. 

They’ve also created the first pigs without the alpha-gal molecule, called the “GalSafe” lineage. Alpha-gal is the sugar found in red meat that causes an allergic reaction for people with alpha-gal syndrome, which is caused by a tick bite. And Revivicor has sent free “GalSafe” bacon, ham and pork chops to people with alpha-gal syndrome, according to the Atlantic. In other words, they’ve created a meat that’s safe to eat for the estimated 450,000 people who might have this allergy. 

Although Revivicor told the Food and Drug Administration ( FDA) the company is considering a mail-order meat business for the alpha-gal afflicted, they are primarily dedicated to raising the pigs for xenotransplantation. 

The company is currently building a giant R&D facility in Christiansburg, Virginia, that will house approximately 200 pigs inside a pathogen-free area, according to the Roanoke Times. It’s likely that the pigs will live in better conditions than those in factory farming, which slaughtered 10 million pigs in the United States in 2022.

Revivicor did not respond to an immediate request for comment.

Further, some question the ethics of keeping a brain-dead patient alive for several weeks, which, in the NYU study, has been permitted by the family but without the individual’s awareness. 

“I feel for them,” Dr. Mohiuddin says. “So ethical concerns, yes, we don't want to be doing anything without patients’ approval, but my focus is mostly on making this procedure viable for humans.”

What's next?

Dr. Mohiuddin utilizes some of Revivicor’s pigs for preclinical studies that are required by the FDA before humans can be considered for a Phase 1 clinical trial. In these studies, his team transplants pig hearts into non-human primates.

The FDA requires him to monitor any disease transmission to make sure the organs used are not carrying any pathogens that could be transmitted to humans.

“So far there is no evidence that any of the pig viruses or pathogens can cause any disease in humans,” Dr. Mohiuddin says. “However, you don't know whether, after getting a transplant, in 20 years some virus which is latent can get activated. So [the FDA] wants us to follow our first few patients to the end and have very proper documentation.” 

His team will follow the primates' progress while they seek their next human candidate, who will be a volunteer who has no other treatment options. The xenotransplantation can therefore qualify for a “compassionate use” provision by the FDA that allows for investigational treatment.

“We are looking for a patient who has a better immune system,” he says. “We are considering what we have learned from our last experiment.”